by C. Scott Bailey, DVM, DACT
Despite much of discussion on the subject, there is still a great disparity in treatment protocols for mismated companion animals in the USA and elsewhere. Numerous treatment protocols are available. Ovariohysterectomy has the advantage of permanently removing the risk of an unwanted pregnancy. Medical treatments have varying side effects depending on the protocol selected, and depend on owner vigilance to prevent future pregnancies. Medical treatment is most often performed in early gestation or mid gestation. Pregnancy termination after fetal ossification (45 days) results in abortion of non-viable or poorly viable fetuses.
Treatment choices should be guided by an animal’s actual risk of pregnancy. In dogs, a vaginal swab and cytologic evaluation provide 2 key pieces of information: 1) Detection of sperm heads on cytology can confirm exposure to a male, and 2) determination of estrus stage at the time or presentation. In a study involving 16 females with known breeding histories, Whitacre and coworkers demonstrated that sperm could be seen microscopically in 100% of cases within 24 hours of breeding and in 75% of cases within 48 hours of breeding, using a modified sampling technique. Determination of estrus stage is also a key component of determining the risk of pregnancy. Bitches with known or suspected exposure to a male during proestrus are at much lower risk of pregnancy than those exposed during estrus. Cytologic diagnosis of proestrus can be further confirmed with serum progesterone concentrations of <2ng/mL. As cats are induced ovulators, serum progesterone will likely be low in unexposed cats (<2ng/mL) and would rise after coitus in exposed cats.
Prior to any treatment, it is important to carefully consider options for treatment. Animals that are not intended to be breeding animals, do not have high risk-factors for spay-associated disease and which are not in show, should undergo ovariohysterectomy in early diestrus/pregnancy. This will prevent future unwanted pregnancies and may decrease the animals’ risk of several diseases, including pyometra, mammary and ovarian neoplasia. Animals which cannot be spayed may be treated medically with a variety of protocols.
Early pregnancy termination
Several protocols have been proposed to medically treat bitches as soon as a mismating occurs. This approach is attractive, but may pose a greater risk to the animal and have lower success rates than other protocols. As a result, most reviewers have recommended against these treatment regimens.
Estrogens have been widely used for this purpose in the past, but potentially severe side-effects should raise concerns. Several reports indicate significant health risks associated with estrogen treatment in dogs and cats, including an increased risk of pyometra, infertility and toxicity.
Pregnancy termination in mid-gestation
In the dog, pregnancy can be readily diagnosed by palpation approximately 30 days after mating, whereas ultrasonographic examination can confirm pregnancy as early as 15-18 days after the LH surge (~10-20 days after mating). Embryos are easily detectable between day 22 and 25 after LH surge. In the queen, ultrasonographic pregnancy diagnosis can be achieved as soon as 11 days after mating and the embryo becomes visible by 14 or 15 days after mating.
At this stage, embryonic fluids and tissues are resorbed by the uterus and few clinical signs are expected in response to medical intervention. A bloody discharge may be seen in bitches and queens after approximately 30 days. Abortion (fetal expulsion) occurs after 40-45 days, when fetal ossification is underway.
Natural prostaglandins can be used to terminate pregnancy beginning 5 days after ovulation, however prior to 25 days, higher doses are required than later in gestation. Hospitalization and careful monitoring of animals are recommended to control side-effects, which tend to be more severe early and diminish during the course of treatment. Side effects may be minimized by using low doses of prostaglandin, or by starting with a lower dose and gradually increasing it. It should be noted that low doses may not induce permanent luteolysis, resulting in loss of only some pups or fetal death followed by mummification. The synthetic prostaglandin cloprostenol has also resulted in effective pregnancy termination, with few side effects.
In both the bitch and queen, prolactin plays a necessary luteotrophic role in pregnancy maintenance. Progesterone can be reduced or eliminated during late pregnancy by administering a dopamine agonist, which inhibits endogenous prolactin secretion.32 However, treatment success for pregnancy termination has been inconsistent in both dogs and cats and dopamine agonists alone are rarely used in companion animals.
Combined Prostaglandin/Dopamine Agonist Regimen
Extensive work by Verstegen and coworkers, demonstrated that a dual approach to pregnancy termination results in reliable efficacy in mid gestation. Low doses of either natural or synthetic prostaglandins result in luteolysis, while dopamine agonists inhibit prolactin release. In a series of studies, administration of cabergoline and cloprostenol resulted in fetal resorption with minimal discharge or unwanted drug-effects in both dogs and cats. Treatment was continued until ultrasonographic confirmation of fetal demise. The above protocol has several distinct advantages over other protocols described: Both prostaglandins and dopamine agonists are readily available in the USA. The combined luteolytic and antiluteotrophic mechanisms decrease dosages of each drug, substantially reducing side effects. The protocols can be instituted around day 25 and result in resorption prior to fetal ossification, when most animals would abort formed fetuses. The use of orally administered dopamine agonists and long-acting, synthetic prostaglandins eliminates the need for frequent examination and hospitalization.
In conclusion, risk for pregnancy should be determined at the time of mismating and ideally pregnancy should be confirmed prior to treatment in order to avoid unnecessary and potentially harmful medical side effects. Treatment choices should be based on the animal’s stage of gestation and availability and should be tailored to minimize side effects as much as possible. A treatment onset between 25 and 30 days and combination of two drugs, including a prostaglandin and dopamine agonist minimize drug dosage and side effects while inducing fetal resorption rather than abortion.